On an established mood visual analogue scale (VAS) PD patients with bilateral STN-DBS reported themselves as better-coordinated, stronger and more contented with their stimulation ON than OFF. When combined into factors, the mood scores of the STN-DBS patients reflected greater alertness and calmness when ON stimulation. STN-DBS patients reported more positive mood on 14/16 mood VAS scales and that completion of cognitive and motor tests required less effort with stimulation ON than OFF. When improvements in motor symptoms were controlled for, STN-DBS patients reported feeling better-coordinated and more contented on the combined factors, but less gregarious (equivalent to more withdrawn) with DBS ON than OFF. Control PD patients reported no differences in mood, effort or fatigue on their two completions of the scales, indicating that there was no effect of completing the scales twice.
These mood ratings are likely to reflect the patients’ day-to-day mood states after STN-DBS. Apart from the improved motor symptoms (discussed in the next paragraph), the 50% reduction in dopaminergic medication post-surgery, which would have reduced ON-state involuntary dyskinesias, is likely to have contributed to the patients’ reports of feeling better-coordinated and stronger with DBS ON. STN-DBS patients also reported feeling more contented with stimulation ON and reported that they needed less effort to complete the intervening cognitive tests, which is consistent with feeling stronger and better co-ordinated.
The analysis of covariance showed that the mood ratings were influenced by the improvement of the motor symptoms rated on the UPDRS-III. The significant stimulation-induced improvements in feeling strong and contented were largely accounted for by improved motor symptoms. Reports of feeling better co-ordinated and requiring less effort for task completion remained significant even after covarying out the UPRDS-III change score. Differences between DBS ON vs OFF became significant for the combined factor of Contented-Discontented, suggesting that patients’ greater sense of contentment with stimulation ON had been masked by variance associated with changes in motor symptoms with stimulation. A decrease in gregariousness, equivalent to an increase in feeling withdrawn, also became significant after covarying out the UPDRS change score. This potentially reflects increased apathy with STN-DBS ON, as reported in other studies4
. The apathy questionnaire used in the current study was only completed with STN-DBS ON, so cannot shed further light on this issue.
The results of the current study are consistent with the few previous studies of the short-term effects of STN-DBS on mood. Bilateral STN-DBS patients with stimulation ON reported less fatigue and mental confusion6
, more activity and euphoria and less sedation and dysphoria7
, and had lower BDI and apathy scores8,18
. Patients with unilateral STN-DBS reported less tiredness but more anger and confusion with stimulation ON5
. All of these studies were done between 3 months and 4 years after surgery.
The VAS used by us has been validated9,10
, was more comprehensive and had better face validity for the patients than measures employed in previous studies4,5,6,7,8,18
. In addition to mood items, the VAS included somatic and alertness items which are relevant to the assessment of STN-DBS effects. We used an unoperated PD control group to ensure that changes in the VAS ratings for the STN-DBS group did not merely reflect the effect of two consecutive assessments. In contrast, the interpretation of the results of this study is limited by the small sample size and the relatively large range of intervals between surgery and testing. Mood may be more labile shortly after STN-DBS surgery3
, and it is possible that our sample may be heterogenous in that respect, although the majority were assessed 6 months or more after surgery when transient mood changes would ordinarily have subsided. DBS can potentially have placebo effects as demonstrated for motor function19,20
which could also influence self-reported mood. While inclusion of the PD control group and counterbalancing of the ratings with DBS ON vs OFF in our study controlled for some confounding factors, placebo effects could have potentially influenced the results and should be addressed in future studies.
Short-term DBS ON versus OFF effects on mood resemble the levodopa-associated non-motor fluctuations experienced by some PD patients who reported anxiety, irritability, fatigue and depression OFF medication which improved ON medication21,22
. Some levodopa-induced non-motor fluctuations, particularly sensory, cognitive and autonomic fluctuations were alleviated with STN-DBS, whereas ‘psychic’ fluctuations were less consistently improved23
. It is interesting to compare the effects of STN-DBS and levodopa on mood in PD, given the difference in localisation/selectivity of action of the two treatments. Both levodopa and STN-DBS improved mental confusion6
, induced feelings of greater activity and euphoria and less dysphoria7
, improved BDI scores8
and reduced apathy scores18
. Levodopa reduced ‘feeling unsafe’6
and increased hedonia scores8
, but STN-DBS had no effect. STN-DBS reduced fatigue6
and feelings of sedation7
while levodopa had no effect. The effects of levodopa in increasing positive mood and activity and reducing confusion are consistent with the known role of mesolimbic dopamine in enhancing reward and stimulus salience24,25
. However, it is not known whether STN-DBS stimulation affects mesolimbic dopamine; and the improvement of mood and activity and reduction of confusion with STN-DBS may be mediated by stimulation of limbic STN regions leading to effects on limbic areas such as the anterior cingulate cortex26
The studies on the short-term effects of STN-DBS on mood indicate that stimulation has a small but generally positive effect on mood in patients for whom STN-DBS improves the motor symptoms of PD. The only point of concern is that STN-DBS patients reported feeling less gregarious (equivalent to more withdrawn) with stimulation ON, after controlling for improved motor symptoms, which may relate to reports of apathy after STN-DBS. The patients in this and previous studies had had STN-DBS relatively recently, so it is not clear whether similarly positive overall short-term effects of stimulation on mood would be replicated 5 or 10 years after surgery. In the short-term our results are clinically useful for reassuring patients that switching STN-DBS on is likely to have mostly beneficial effects on mood and sense of well-being. However, these group effects may not apply to all individuals, as Czernicki et al.18
found individual differences in short-term STN-DBS effects on apathy. Furthermore, Okun et al.5
reported that unilateral stimulation more ventrally in the STN worsened mood, suggesting that electrode positioning in the STN may be important.
A better understanding of the short-term effects of STN-DBS stimulation on a wide range of mood states could contribute to improved clinical management of patients with STN-DBS and potentially to our understanding of the longer-term effects of DBS. A number of aspects require further study. The time course of the short-term effect of STN-DBS on mood is not known as all studies so far, including this one, have assessed patients with STN-DBS at a single time-point. There may be transient mood effects in the first weeks and months after STN-DBS surgery27
, whereas slow development of longer-term mood problems may also occur28
. If the time-course of the short-term effects of STN-DBS on mood was known, it could perhaps be used as a predictor of longer-lasting mood problems after surgery, allowing pre-emptive treatment and giving some insight into the development of longer-term neural adaptation to STN-DBS. Evaluation of mood states with a strong motivational element, such as enthusiasm, interest and engagement, may be particularly important because of concerns about the longer-term association of STN-DBS with apathy28
. Similarly, evaluation of the short-term effects of STN DBS on impulsivity may clarify impulsive decision-making reported with DBS ON versus OFF29
and the increased suicide risk following surgery30